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      Analysis of the protective efficacy of approved COVID-19 vaccines against Omicron variants and the prospects for universal vaccines

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          Abstract

          By the end of 2022, different variants of Omicron had rapidly spread worldwide, causing a significant impact on the Coronavirus disease 2019 (COVID-19) pandemic situation. Compared with previous variants of severe acute respiratory syndrome coronavirus 2 (SARS–CoV-2), these new variants of Omicron exhibited a noticeable degree of mutation. The currently developed platforms to design COVID-19 vaccines include inactivated vaccines, mRNA vaccines, DNA vaccines, recombinant protein vaccines, virus-like particle vaccines, and viral vector vaccines. Many of these platforms have obtained approval from the US Food and Drug Administration (FDA) or the WHO. However, the Omicron variants have spread in countries where vaccination has taken place; therefore, the number of cases has rapidly increased, causing concerns about the effectiveness of these vaccines. This article first discusses the epidemiological trends of the Omicron variant and reviews the latest research progress on available vaccines. Additionally, we discuss progress in the development progress and practical significance of universal vaccines. Next, we analyze the neutralizing antibody effectiveness of approved vaccines against different variants of Omicron, heterologous vaccination, and the effectiveness of multivalent vaccines in preclinical trials. We hope that this review will provide a theoretical basis for the design, development, production, and vaccination strategies of novel coronavirus vaccines, thus helping to end the SARS-CoV-2 pandemic.

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          SARS-CoV-2 vaccines in development

          Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in late 2019 in China and is the causative agent of the coronavirus disease 2019 (COVID-19) pandemic. To mitigate the effects of the virus on public health, the economy and society, a vaccine is urgently needed. Here I review the development of vaccines against SARS-CoV-2. Development was initiated when the genetic sequence of the virus became available in early January 2020, and has moved at an unprecedented speed: a phase I trial started in March 2020 and there are currently more than 180 vaccines at various stages of development. Data from phase I and phase II trials are already available for several vaccine candidates, and many have moved into phase III trials. The data available so far suggest that effective and safe vaccines might become available within months, rather than years.
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            Development of an inactivated vaccine candidate for SARS-CoV-2

            The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. There are currently no SARS-CoV-2-specific treatments or vaccines available due to the novelty of the virus. Hence, rapid development of effective vaccines against SARS-CoV-2 are urgently needed. Here we developed a pilot-scale production of a purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc), which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats and non-human primates. These antibodies neutralized 10 representative SARS-CoV-2 strains, suggesting a possible broader neutralizing ability against SARS-CoV-2 strains. Three immunizations using two different doses (3 μg or 6 μg per dose) provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without observable antibody-dependent enhancement of infection. These data support clinical development of SARS-CoV-2 vaccines for humans.
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              Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on covid-19 related symptoms, hospital admissions, and mortality in older adults in England: test negative case-control study

              Objective To estimate the real world effectiveness of the Pfizer-BioNTech BNT162b2 and Oxford-AstraZeneca ChAdOx1-S vaccines against confirmed covid-19 symptoms (including the UK variant of concern B.1.1.7), admissions to hospital, and deaths. Design Test negative case-control study. Setting Community testing for covid-19 in England. Participants 156 930 adults aged 70 years and older who reported symptoms of covid-19 between 8 December 2020 and 19 February 2021 and were successfully linked to vaccination data in the National Immunisation Management System. Interventions Vaccination with BNT162b2 or ChAdOx1-S. Main outcome measures Primary outcomes were polymerase chain reaction confirmed symptomatic SARS-CoV-2 infections, admissions to hospital for covid-19, and deaths with covid-19. Results Participants aged 80 years and older vaccinated with BNT162b2 before 4 January 2021 had a higher odds of testing positive for covid-19 in the first nine days after vaccination (odds ratio up to 1.48, 95% confidence interval 1.23 to 1.77), indicating that those initially targeted had a higher underlying risk of infection. Vaccine effectiveness was therefore compared with the baseline post-vaccination period. Vaccine effects were noted 10 to 13 days after vaccination, reaching a vaccine effectiveness of 70% (95% confidence interval 59% to 78%), then plateauing. From 14 days after the second dose a vaccination effectiveness of 89% (85% to 93%) was found compared with the increased baseline risk. Participants aged 70 years and older vaccinated from 4 January (when ChAdOx1-S delivery commenced) had a similar underlying risk of covid-19 to unvaccinated individuals. With BNT162b2, vaccine effectiveness reached 61% (51% to 69%) from 28 to 34 days after vaccination, then plateaued. With ChAdOx1-S, effects were seen from 14 to 20 days after vaccination, reaching an effectiveness of 60% (41% to 73%) from 28 to 34 days, increasing to 73% (27% to 90%) from day 35 onwards. On top of the protection against symptomatic disease, a further 43% (33% to 52%) reduced risk of emergency hospital admission and 51% (37% to 62%) reduced risk of death was observed in those who had received one dose of BNT162b2. Participants who had received one dose of ChAdOx1-S had a further 37% (3% to 59%) reduced risk of emergency hospital admission. Follow-up was insufficient to assess the effect of ChAdOx1-S on mortality. Combined with the effect against symptomatic disease, a single dose of either vaccine was about 80% effective at preventing admission to hospital with covid-19 and a single dose of BNT162b2 was 85% effective at preventing death with covid-19. Conclusion Vaccination with either one dose of BNT162b2 or ChAdOx1-S was associated with a significant reduction in symptomatic covid-19 in older adults, and with further protection against severe disease. Both vaccines showed similar effects. Protection was maintained for the duration of follow-up (>6 weeks). A second dose of BNT162b2 was associated with further protection against symptomatic disease. A clear effect of the vaccines against the B.1.1.7 variant was found.
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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/1403656Role: Role: Role:
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                URI : https://loop.frontiersin.org/people/2087607Role: Role: Role:
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                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                27 November 2023
                2023
                : 14
                : 1294288
                Affiliations
                [1] 1 Shulan International Medical College, Zhejiang Shuren University , Hangzhou, China
                [2] 2 School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University , Hangzhou, China
                [3] 3 Department of Virus Inspection, Zhejiang Provincial Center for Disease Control and Prevention , Hangzhou, China
                Author notes

                Edited by: Salman Sadullah Usmani, Albert Einstein College of Medicine, United States

                Reviewed by: Larry Ellingsworth, Novavax, Inc., United States; Güliz Tuba Barut, Institute of Virology and Immunology, Switzerland

                *Correspondence: Yanjun Zhang, yjzhang@ 123456cdc.zj.cn ; Jianhua Li, jhli@ 123456cdc.zj.cn

                †These authors have contributed equally to this work and share the first authorship

                Article
                10.3389/fimmu.2023.1294288
                10711607
                38090587
                e45a2d53-4f1b-4bb8-9c85-52ff12d17544
                Copyright © 2023 Chen, Zhang, Fang, Li, Li, Song, Huang, Chen, Zhang and Li

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 14 September 2023
                : 01 November 2023
                Page count
                Figures: 3, Tables: 1, Equations: 0, References: 105, Pages: 22, Words: 15244
                Funding
                The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants from the Opening Foundation of State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University [grant number SKLID2020KF0420]; the Major Horizontal Project of Zhejiang Shuren University [grant number 2020D1284]; the National Innovation and Entrepreneurship Training Program for College Students in 2023 [grant number 202311842005X]; and the Key Research and Development Program of Zhejiang Province [program number 2021C03044].
                Categories
                Immunology
                Review
                Custom metadata
                Vaccines and Molecular Therapeutics

                Immunology
                sars-cov-2,covid-19,omicron variants,vaccine effectiveness,convergent evolution,universal vaccines

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